Bacitracin is a water-soluble unstable cyclic polypeptide produced by cultivation of B. subtilis or B. licheniformis on a submerged nutrient medium under aerobic conditions and is particularly effective against gram-positive microorganisms. Bacitracin is widely, nearly exclusively, used for animal feed purposes; this aspect of its use is believed to be more important than its use in human therapy. It exerts an influence on the intestinal flora of the animals. When used as a feed supplement it promotes growth of the young animals and the utilization of the feed. It is the only antibiotic which does not inhibit the functioning of the micro flora of the digestive tract of ruminants even in large doses, but inhibits the reproduction of pathogenic microorganisms. Its use is particularly advantageous since it is not absorbed and cannot be detected in the animal products (meat, milk etc.). Because it is not used for therapeutic purposes the problem of developed resistance is negligible.
Bacitracin produced by fermentation is very unstable in a pure stage it is very complicated to prepare bacitracin from the available dilute solution formulations. Several methods are known for the preparation of products of high bacitracin content.
According to the methods described for example in U.S. Pat. Nos. 2,582,921; 2,457,887 and 2,739,063 bacitracin is precipitated from dilute solutions on inorganic carriers. The common feature of these methods is the low yield and the instability of the product.
In accordance with other known methods bacitracin is recovered by extraction with organic solvents as described in U.S. Pat. Nos. 2,498,165 and 2,609,324. These methods involve the disadvantage that large amounts of solvent are required, the solvents must be regenerated, the yield is low and the extraction is not selective.
According to further known methods (U.S. Pat. Nos. 2,776,240 and 2,915,432) bacitracin is recovered by ion-exchange sorption. It is a deficiency of these methods however, that the yield is low and the technology is complicated.
The isolation of bacitracin in the form of complexes is described in U.S. Pat. Nos. 2,556,375, 2,774,712 and 3,035,919, Czechoslovak Pat. No. 119,180 and Hungarian Pat. No. 157,983. These methods are less complicated than those mentioned before and the bacitracin content of the product is higher but the precipitating agents are expensive and some of them have analgetic properties.
Bacitracin can be isolated in the form of a complex by means of Zn, Mn, Ni or Co salts (U.S. Pat. Nos. 2,809,892; 3,025,216; 2,903,357; 2,985,533; 2,985,534 and 3,021,217). In accordance with U.S. Pat. No. 2,809,892 a water-soluble zinc salt is added to the acidified fermentation liquor of bacitracin, zinc bacitracin is precipitated by raising the pH of the mixture, the zinc bacitracin complex is separated and the separated complex is dried. The metal complexes obtained are stable but the bacitracin content does not exceed 4 to 8 % owing to the co-precipitation of the metal hydroxides and complicated methods, e.g. ion exchange sorption are needed to purify the product (U.S. Pat. No. 2,834,711).